Early biochemical events associated with lymphocyte activation in ageing. I. Evidence that Ca2+ dependent processes induced by PHA are impaired.
The requirement for Ca2+, a divalent ion which plays a fundamental role in cell activation, has been analysed in cultures of PHA-stimulated human peripheral blood lymphocytes (PHA-PBL) from adult (range: 20-35 years) and old (over 70 years) subjects. For this purpose, increasing concentrations of Ca2+ chelators (EGTA and EDTA) were added to cultures in order to compare the effect of progressive extracellular Ca2+ (Ca2+EC) depletion on [3H]-Tdr incorporation by PHA-PBL. Kinetic analysis showed that Ca2+EC requirement was restricted to the first 24 h after culture initiation. At optimal doses of PHA, the PHA-PBL from old subjects were more sensitive than those from adult subjects to increasing concentrations of both chelators. They also required larger amounts of Ca2+ supplements to restore their normal response after total inhibition by EGTA. Furthermore, the PHA-PBL from the elderly were hypersensitive to verapamil (Isoptin), a drug which instigates a reversible inhibition of Ca2+-dependent processes associated with lymphocyte transformation, by a quite similar reaction to that induced by chelators. We conclude that the Ca2+-dependent processes in lymphocyte activation are impaired with ageing. Following further experiments and recent work suggesting that lymphocytes need more than one signal to proliferate, the authors speculate on a deficiency of a late activation signal requiring cell-cell interactions in the elderly.
D000328:Adult; D000368:Aged; D000375:Aging; D002118:Calcium / Q000502:physiology*; D002478:Cells, Cultured; D004306:Dose-Response Relationship, Immunologic; D004492:Edetic Acid / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D005260:Female; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D010835:Phytohemagglutinins / Q000494:pharmacology; D013936:Thymidine / Q000378:metabolism; D013997:Time Factors; D014700:Verapamil / Q000494:pharmacology
D010835:Phytohemagglutinins; D004533:Egtazic Acid; D004492:Edetic Acid; D014700:Verapamil; D002118:Calcium; D013936:Thymidine